Habitual abortion means a condition in which pregnancy is established, but spontaneous abortion and stillbirth are repeated. Causes of habitual abortion are manifold, and abnormal immunological functions are considered to be one of the causes.
As a means to diagnose habitual abortion caused by auto-immunity, there is known a method of determining an auto-antibody, anti-cardiolipin antibody (recently, the antigen of this auto-antibody was demonstrated to be a complex of cardiolipin and β2-glycoprotein I (β2-GPI), and has been designated as β2-GPI-dependent anti-caridiolipin antibody).
However, the above method was not completely reliable, and even a negative result of the assay could not rule out the possibility of habitual abortion. Furthermore, even when the measurement of another marker was combined, satisfactory results could not be obtained. Thus, there has been a need for the development of novel markers different from existing markers.
Also, situations in sterility, infertility, and endometriosis have been similar to those in habitual abortion, and there has been a need for the development of markers that are simpler to determine and are highly reliable.
Laminin is a glycoprotein most abundant in the basement membrane, and is forming a complex with other components of the basement membrane such as nidogen and type IV collagen. Laminin takes the form of an asymmetric cross in which three polypeptides are combined in a coiled form, and the presence of many isoforms has been confirmed. Thus, combinations of three polypeptides, α chain (about 400 kDa), β chain (about 200 kDa) and γ chain (about 200 kDa), that constitute laminin could lead to the formation of various isoforms, and until now the presence of at least 12 isoforms has been reported (J. Cell Biol., 137, 685–701 (1997); J. Cell Biol., 145, 605–618 (1999)).
For example, it has been demonstrated that laminin-1 (α1, β1, γ1) occurs in the kidney, the fetal rain, the retina, blood vessels etc., merosin (=laminin-2; α2, β1, γ1) occurs in the skeletal muscle, the heart, the placenta etc., s-laminin (=laminin-3; α1, β2, γ1) occurs in the basement membrane of the junction of neuromuscular ending plate, endothelium and glomerular basement membrane, s-merosin (=laminin-4; α2, β2, γ1) occurs in Schwann cells, the placenta etc., kalinin/nicein (=laminin-5; α3, β3, γ2) and k-laminin (=laminin-6; α3, β1, γ1) and ks-laminin (=laminin-7; α3, β2, γ1) are peculiar to the basement membrane of the skin.
The detection of such laminin or a fragment thereof, it has been reported, is likely to be used for the diagnosis of various diseases such as hepatic fibrosis/cirrhosis, alcoholic hepatic fibrosis, diabetic complications, kidney diseases, chronic polyarthritis, tumors, and Alzheimer's disease.
Also, for anti-laminin-1 antibody that is an auto-antibody against laminin, it has been reported that anti-laminin antibody can be detected in the serum of monkeys that tend to abort easily, that the addition of serum containing anti-laminin antibody into rat's fetus causes anomalies in the fetus, that immunization of anti-laminin antibody into mice can induce abortion, and the like (Fertil. Steril, 51, 711–718 (1989); Teratology 40, 47–57 (1989); Proc. Natl. Acad. Sci. USA, 92, 6818–6822 (1995); Am. J. Pathol., 110, 346–357 (1983)), and therefore-anti-laminin antibody has been estimated to be one of the factors responsible for abortion.
However, for the significance of determination of anti-laminin antibody in humans, it has only been reported that the assay of auto-antibody against laminin with a molecular weight of 200 kDa that specifically occurs in the urine but not in the serum may be used for the diagnosis of systemic lupus erythematosus (SLE) (Japanese Unexamined Patent Publication (Kokai) No. 8-36966; J. Autoimmun., 8(2), 279–291 (1995)), and no suggestion has been made on whether or not it can be used for the diagnosis of gynecology-related diseases such as habitual abortion, sterility, infertility, and endometriosis.